Comparative Assessment of the Structural Features of Originator Recombinant Human Follitropin Alfa Versus Recombinant Human Follitropin Alfa Biosimilar Preparations Approved in Non-European Regions

oleh: Lucio Manzi, Nunzio Sepe, Walter Migliaccio, Ludovica Lanzoni, Luisa Iozzino, Fabrizia D’Angelo, Lucia Colarusso, Susana Montenegro, Angelo Palmese, Thomas D’Hooghe, Alfredo Ulloa-Aguirre, Yulia Koloda, Monica Lispi

Format: Article
Diterbitkan: MDPI AG 2022-06-01

Deskripsi

Although the full primary structures of the alfa and beta subunits of reference r-hFSH-alfa and its biosimilars are identical, cell context-dependent differences in the expressing cell lines and manufacturing process can lead to variations in glycosylation profiles. In the present study, we compared the structural features of reference r-hFSH-alfa with those of five biosimilar preparations approved in different global regions outside Europe (Primapur<sup>®</sup>, Jin Sai Heng<sup>®</sup>, Follitrope<sup>®</sup>, Folisurge<sup>®</sup>, and Corneumon<sup>®</sup>) with respect to glycosylation, macro- and microheterogeneity, and other post-translational modifications and higher order structure. The mean proportion of <i>N</i>-glycosylation-site occupancy was highest in reference r-hFSH-alfa, decreasing sequentially in Primapur, Jin Sai Heng, Corneumon, Follisurge and Follitrope, respectively. The level of antennarity showed slightly higher complexity in Corneumon, Primapur and Follitrope versus reference r-hFSH-alfa, whereas Jin Sai Heng and Folisurge were aligned with reference r-hFSH-alfa across all <i>N</i>-glycosylation sites. Sialylation level was higher in Corneumon and Follitrope, but small differences were detected in other biosimilar preparations compared with reference r-hFSH-alfa. Jin Sai Heng showed higher levels of <i>N</i>-glyconeuramic acid than the other preparations. Minor differences in oxidation levels were seen among the different products. Therefore, in summary, we identified var ious differences in <i>N</i>-glycosylation occupancy, antennarity, sialylation and oxidation between reference r-hFSH-alfa and the biosimilar preparations analyzed.